Lipid Signalling in the Pathology of Autism Spectrum Disorders

Wong, Christine; Crawford, Dorota A.

doi:10.1007/978-1-4614-4788-7_68

Cited by 17 publications

(28 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This review describes for the first time the possible mechanisms by which the PGE 2 signaling pathway can be affected in the fetal brain during critical stages of development. Abnormal PGE 2 signaling in the prenatal brain may result from changes in the maternal PGE 2 level due to deficient dietary supplementation, increased exposure to drugs, oxidative stress, infections and inflammation (Tamiji & Crawford, ,b; Wong & Crawford, ). Maternal PGE 2 may access the developing brain through diffusion across cell membranes via its hydrophobic property or by passing across protective barriers through specific transporters summarized above.…”

Section: Protective Barriersmentioning

confidence: 99%

“…Fatty acids are the simplest form of lipids that serve as the building blocks for more complex lipids, such as phospholipids, cholesterol and vitamin E. A sufficient supply and balance of fatty acids is integral to cell membrane integrity, which is an indicator for healthy development, maintenance and function of the nervous system (Lawrence, ). Environmental factors such as diet, increased levels of oxidative stress, and exposure to infections and inflammation can lead to altered lipid metabolism (Adibhatla & Hatcher, ; Tamiji & Crawford, ,b; Wong & Crawford, ).…”

Section: Introductionmentioning

confidence: 99%

“…It has previously been described that abnormal PGE 2 signaling [which can result from genetic defects or exposure to environmental factors, including deficient dietary supplementation, increased exposure to drugs (i.e. prostaglandin E analog, misoprostol), oxidative stress, infections and inflammation] has been highly implicated in the etiology of ASDs (Tamiji & Crawford, ,b; Wong & Crawford, ). This review provides a unique summary of additional common environmental risk factors capable of directly or indirectly disrupting PGE 2 signaling, such as air pollutants, compounds found in food products and personal care products like cosmetics.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders

Wong

Wais

Crawford

2015

Eur J of Neuroscience

View full text Add to dashboard Cite

The prevalence of autism spectrum disorders (ASDs) has been on the rise over recent years. The presence of diverse subsets of candidate genes in each individual with an ASD and the vast variability of phenotypical differences suggest that the interference of an exogenous environmental component may greatly contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2 ) is released from phospholipids of cell membranes, and is important in brain development and function; PGE2 is involved in differentiation, synaptic plasticity and calcium regulation. The previous review already described extrinsic factors, including deficient dietary supplementation, and exposure to oxidative stress, infections and inflammation that can disrupt signaling of the PGE2 pathway and contribute to ASDs. In this review, the structure and establishment of two key protective barriers for the brain during early development are described: the blood-brain barrier; and the placental barrier. Then, the first comprehensive summary of other environmental factors, such as exposure to chemicals in air pollution, pesticides and consumer products, which can also disturb PGE2 signaling and increase the risk for developing ASDs is provided. Also, how these exogenous agents are capable of crossing the protective barriers of the brain during critical developmental periods when barrier components are still being formed is described. This review underlines the importance of avoiding or limiting exposure to these factors during vulnerable periods in development.

show abstract

Section: Protective Barriersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders

Wong

Wais

Crawford

2015

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…Current research on the developing brain has provided substantial evidence for the link between ASD and abnormal signaling of the lipid mediator, prostaglandin E2 (PGE2) . PGE2 is the major lipid molecule in the nervous system.…”

Section: Introductionmentioning

confidence: 99%

Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

Wong

Bestard-Lorigados

Crawford

2018

Genes Brain and Behavior

View full text Add to dashboard Cite

Prostaglandin E2 (PGE2) is an endogenous lipid molecule involved in normal brain development. Cyclooxygenase-2 (COX2) is the main regulator of PGE2 synthesis. Emerging clinical and molecular research provides compelling evidence that abnormal COX2/PGE2 signaling is associated with autism spectrum disorder (ASD). We previously found that COX2 knockout mice had dysregulated expression of many ASD genes belonging to important biological pathways for neurodevelopment. The present study is the first to show the connection between irregular COX2/PGE2 signaling and autism-related behaviors in male and female COX2-deficient knockin, (COX)-2 , mice at young (4-6 weeks) or adult (8-11 weeks) ages. Autism-related behaviors were prominent in male (COX)-2 mice for most behavioral tests. In the open field test, (COX)-2 mice traveled more than controls and adult male (COX)-2 mice spent less time in the center indicating elevated hyperactive and anxiety-linked behaviors. (COX)-2 mice also buried more marbles, with males burying more than females, suggesting increased anxiety and repetitive behaviors. Young male (COX)-2 mice fell more frequently in the inverted screen test revealing motor deficits. The three-chamber sociability test found that adult female (COX)-2 mice spent less time in the novel mouse chamber indicative of social abnormalities. In addition, male (COX)-2 mice showed altered expression of several autism-linked genes: Wnt2, Glo1, Grm5 and Mmp9. Overall, our findings offer new insight into the involvement of disrupted COX2/PGE2 signaling in ASD pathology with age-related differences and greater impact on males. We propose that (COX)-2 mice might serve as a novel model system to study specific types of autism.

show abstract

“…Defects in dendrite morphogenesis are common anatomical features of many neurodevelopmental disorders (Kaufmann and Moser, 2000). Although abnormal lipid metabolism has been observed in mouse models as well as patients with neurodevelopmental disorders (Buchovecky et al, 2013; Tamiji and Crawford, 2010; Tint et al, 1994) and 60 percent of the human brain dry mass is lipids (Wong and Crawford, 2014), relatively little is known about the importance of lipid homeostasis for dendrite morphogenesis during neural development.…”

Section: Introductionmentioning

confidence: 99%

Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

et al. 2017

View full text Add to dashboard Cite

Summary Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas), which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE) synthesis, and two other enzymes in this synthesis pathway are required cell-autonomously in sensory neurons for dendrite growth and stability. Further, we show that the level of Sterol Regulatory Element Binding Protein (SREBP) activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

show abstract

Lipid Signalling in the Pathology of Autism Spectrum Disorders

Cited by 17 publications

References 138 publications

Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders

Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders

Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model

Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

Contact Info

Product

Resources

About